Reply

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We thank Zhang and Song for their interest in our work. While we proposed that the role of Ulk1/2 in APAP‐induced liver injury is independent of general autophagy, selective degradation of mitochondria was not investigated in particular in our study. It is well accepted that degradation of p62 is one of the hallmarks of autophagy activation and APAP‐induced liver injury.1 In our study, we repeatedly observed that APAP treatment leads to the down‐regulation of the protein level of p62 in isolated hepatocytes. These data are consistent with the results obtained both in vivo and in primary hepatocytes by several other groups.2 For example, Lin et al. found that p62 is not accumulated, but instead strongly down‐regulated during APAP treatment in mouse livers,2 with a very similar APAP treatment condition to that in the work by Shen et al.5 Ni et al. also demonstrated that treatment of hepatocytes with APAP drastically leads to degradation of p62.3 It is possible that the unexpected increase in the p62 signal reported by Shen et al. was caused by antibody preference for a specific posttranslationally modified form of p62. Considering p62 could be not only a marker, but also functionally required for APAP‐induced autophagy,3 we agree that investigation of the posttranslational modification of p62 in APAP‐treated Ulk1/2 knockout mice would provide additional information on the protective role of Ulk1/2 in APAP‐induced liver injury.